Human Papillomavirus Infection and Biomarkers in Esophageal Squamous Cell Carcinoma Patients of Pakistan
Authors
Dr Yumna Adnan, Dr Syed Muhammad Adnan Ali
Affiliations
Department of Surgery, Medical College, The Aga Khan University, Pakistan
Introduction
Esophageal cancer is the 11th most common cancer in the world and ranks 7th in cancer-related mortality. Esophageal squamous cell carcinoma (ESCC) makes up the majority of esophageal cancer cases and is marked by a poor prognosis with 5-year survival rate of approximately 15%-25%. Human Papilloma Virus (HPV) has been studied for a possible etiologic role in ESCC, in combination with p16 expression. Various other biomarkers have also been implicated for their role in ESCC, such as Cyclin D1, Cyclooxygenase-2 (COX2), and Epidermal Growth Factor Receptor (EGFR). The aim of this study was to determine HPV infection status and expression of p16, COX2, Cyclin D1 and EGFR in ESCC patients of Pakistan.
Methods
102 ESCC patients treated at Aga Khan University Hospital (AKUH) were included. HPV infection status was confirmed via PCR using HPV general primers and HPV type 16 and type 18 primers once HPV positivity was established. The expression of the four biomarkers was determined via immunohistochemistry using clone H11 for EGFR (Dako), CX-294 for COX2 (Dako), EP12 for Cyclin D1 (Dako) and CINtec p16 E6H4 for p16 (Roche Ventana).
Results
HPV was positively detected in 17 cases, out of which 14 were HPV type16 and 3 were HPV type 18. Contrarily, p16 was found expressed in 37 cases, out of which 5 cases did not have HPV infection. COX2, Cyclin D1 and EGFR were overexpressed in 57%, 63% and 49% of the patients respectively. COX2 showed a significant correlation with tumour invasion while EGFR was shown to be significantly correlated with histological grading and positive COX2 expression. HPV infection was not significantly associated with patient survival.
Conclusion
COX2 and EGFR may be used as prognostic and therapeutic markers for ESCC. HPV may be a causative agent for ESCC in Pakistan.